The HPA axis relies on a series of hormonal signals to keep the sympathetic nervous system — the "gas pedal" of the body — pressed down.

The HPA axis works as follows. When the brain perceives danger (stress) it signals the hypothalamus (the “control centre” of the stress response) to release corticotrophin-releasing hormone CRH which travels to the pituitary gland, triggering the release of adrenocorticotropic hormone (ACTH). This substance travels to the adrenal glands, prompting them to release into the bloodstream of another key-substance: cortisol, also known as “the stress hormone”. When the threat passes, stress-hormones levels, including cortisol, fall. The parasympathetic nervous system — the "brake" — then dampens the stress response.

Unfortunately, this cascade of hormones can be retriggered by another stressful event. This is very popular nowadays: we live in a perpetual state of biochemical stress also known as “allostatic overload” (with stress-hormones secreting constantly so the stress response always activated) because the body overreact to stressors that are not life threatening such as traffic jams, work pressure, and family difficulties.

According to the endocrinologist Hans Selye, stress is a state of threatened homeostasis. During a stressful moment we are out of balance because of the effort - the set of biochemical reactions -our body is carry on to cope with the stressor. From a biological point of view it is common for the body to produce hormonal imbalances – like the stress response - with the purpose to restore homeostasis. This process is known also as “allostatic response”.

Short-lived stress can usually be dealt with, and such as, does not adversely compromised our health. Instead chronic stress - because of the overproduction of stress-substances - upset homeostasis and harm internal organs, leaving the body vulnerable to disease.

Adaptogens fine-tune the body stress response by affecting the feedback control mechanism making it more responsive/adaptive so that the feedback response (stress-hormones release) is cut off faster. Specifically adaptogens inhibit the production of CRH and ACTH from the hypothalamus and pituitary, reducing the output of stress hormones.

This means that the stress hormones don’t ramp up with each stressful event, allowing you to meet life’s challenges with less tension and anxiety, more energy and greater mental clarity. For that reason adaptogens are “stress-agonist” and not stress-antagonist. Adaptogens do not operate on the stressors but on out ability to deal with it (adaptability).

In this sense, adaptogens offer a natural action able to enhance the ability of an organism to increase resistance to a broad spectrum of harmful factors and to avoid damage from such factors.

To understand the adaptogenic effect may help this graphic below showing the effect on the sympathetic systems.

As showed by the graphic, the sympathetic nervous system functions like a gas pedal in a car. It triggers the “fight-or-flight” response, the release of hormones that help us to cope with the stressor.

The sympathetic nervous system is part of the “autonomic nervous system” which is responsible for regulating the body's unconscious actions. The sympathetic nervous system works in couple with the parasympathetic nervous system. The parasympathetic nervous system acts like a brake. It promotes the "rest and digest" response that calms the body down (decrease of stress-hormones) after the danger has passed.

The state of the body at any given time represents a balance between the sympathetic and parasympathetic systems.

In case of overproduction of stress-hormones and by including adaptogenic phytochemical in our blood, the stress response will be re-modulated so homeostasis will be restore more quickly and efficiently (B). In absence of adaptogenic phytonutrients (A) stressors tend to prevail thus the release of stress-hormones will be prolonged affecting our homeostasis.

A series of recent pharmacological studies have proven adaptogens effects at the molecular level. The stress protective activity of adaptogens has been found to be associated with activation of molecular chaperonin Hsp 120 and other key mediators of the stress response such as nitric oxide, stress-activated protein kinase JNK, DAF 16 and cortisol. Studies have demonstrated that heat-shock factor 1 (HSF1) and Neuropeptide Y might be primary upstream molecular targets of adaptogens in neuroglia cells (or “glia cells”) which are non-neuronal cells that maintain homeostasis, form myelin, and provide support and protection for neurons in the central and peripheral nervous systems.

Adaptogens have also immunomodulating or immunostimulating properties. An “immunomodulator” or “immune amphoteric” affects the immune system due to its ability to modify or regulate immune function. Long-term stress decreases the number of white blood cells, which are involved in protecting the body against both infectious disease and foreign invaders. When stress turns chronic, then the immune system begins to be impaired. Specifically any type of stress has a harmful effect on the ability to maintain optimal levels of NK-cell activity. Natural killer cells or NK cells are a type of immune cells unique as they have the ability to recognize stressed cells allowing for a much faster immune reaction.

Adaptogens help to counter chronic immune cell depletion and improve the body’s defences by increasing the production of specialized cells including helper T cells, B cells and NK cells.

Repeated dose administration of adaptogens has been shown to be of value in sports medicine and can lead to increased endurance (stamina) or to a more rapid recovery from a stressor event. However the stress protective effect by repeated intake is not the result of inhibition of the stress response, but of adaptive changes in the organism to the repeated stress-mimetic effect of the drug.